Is MET p.Val37Ala (c.110T>C) pathogenic?

MET p.Val37Ala (c.110T>C) is classified Benign/Likely benign in MET (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.1306); Rare (popmax 0.687%, sas); Associated with renal cell carcinoma.

What condition is associated with MET p.Val37Ala (c.110T>C)?

MET p.Val37Ala (c.110T>C) is associated with renal cell carcinoma, hereditary neoplastic syndrome (ClinVar).

How common is MET p.Val37Ala (c.110T>C) in the general population?

MET p.Val37Ala (c.110T>C) is rare (popmax 0.687%, sas) (gnomAD).

What do computational predictors say about MET p.Val37Ala (c.110T>C)?

AlphaMissense predicts likely benign (score 0.1306) — an in-silico prediction, not a clinical call.

MET p.Val37Ala

c.110T>C · rs201315884 · VCV41610

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

AlphaMissense

likely benign

0.1306 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.687%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

renal cell carcinoma

Computational evidence

Protein change
AlphaMissense	0.1306	likely benign
REVEL	0.142	moderately benign-leaning
SaProt	LLR -6.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.7, phastCons 1
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.687% South Asian · 626/91,078 alleles

Filtering AF 0.643% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.625%

Overall 0.0545% 879/1,613,956 alleles · rare exomes 841/1,461,710 · genomes 38/152,246 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.687%	145
Middle Eastern	0.149%	673
Ashkenazi Jewishnot grpmax-eligible	0.122%	822
Remaining individualsnot grpmax-eligible	0.0736%	1,359
European (non-Finnish)	0.0133%	7,515
Admixed American	0.005%	19,993
African / African-American	0.00267%	37,511

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: MET
Protein: p.Val37Ala
Coding: c.110T>C
MANE Select: NM_000245
dbSNP: rs201315884
Type: single nucleotide variant
Location: chr7:116699194 (GRCh38)
Gene constraint: LOEUF 0.446 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.28 · 130 PDB
Residue 37: the sema domain

Full MET gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

renal cell carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

Similar variants

MET p.Val37Gly Uncertain significance ★ ⚠ same residue
MET p.Val37Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
MET p.His1094Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
MET p.Met1131Thr Pathogenic/Likely pathogenic ★★ same condition
MET p.Val1092Ile Pathogenic/Likely pathogenic ★★ same condition
MET p.Val1220Ile Pathogenic/Likely pathogenic ★★ same condition
MET c.1200+2T>C Uncertain significance ★★ same condition
MET c.1392+1G>T Uncertain significance ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/met-p-val37ala (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown